This proposal from the University of California, San Francisco (UCSF) responds to RFA HL-14-014 for Clinical Centers for the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, with a commitment to enroll 40 patients annually in clinical trials based in the Emergency Departments and the Intensive Care Units. The Principal Investigator will be Michael A. Matthay, MD, Professor of Medicine & Anesthesia at UCSF and the Co-Investigator will be Greg Hendey, MD, Professor and Chair, Emergency Medicine, UCSF-Fresno. There will be four participating hospitals that have an established track record of effective communication, collaboration and patient recruitment as part of the Acute Respiratory Distress Syndrome (ARDS) Network 2: (1) UCSF Moffitt-Long Hospital, the major teaching hospital at UCSF; (2) UCSF Fresno/Community Regional Medical Center, a major medical center caring for patients in the Central Valley of California located in Fresno, CA; (3) University of California, Davis Medical Center; and (4) Stanford University Medical Center. Thus, the California Network will be comprised of four major medical centers in Northern California that draw from a total population of approximately 12 million people. Each site has an established and highly motivated research coordinator and critical care investigator with experience in ARDS Network 2. To be responsive to this RFA, each site has added an Emergency Department investigator with significant prior experience in clinical trials. In addition to our work as part of ARDS Network 2 and with Emergency Department-based clinical trials, the California Network has significant expertise that is highly relevant to the current RFA. We have a major research focus on clinical criteria to identify patients at risk for ARDS prior to the initiation of positive pressure ventilation as well as a longstanding preclinical and clinical focu on novel therapeutics for ARDS. In fact, Dr. Matthay is the Principal Investigator for an ongoing NHLBI-funded phase 1/2a clinical trial of allogeneic, bone marrow-derived human mesenchymal stem cells for patients with moderate to severe ARDS that will be completed prior to the start of the PETAL Network. We are proposing two clinical protocols, one for patients with early lung injury prior to the development of ARDS that can be identified in the Emergency Department and one for patients in the Intensive Care Unit for severe ARDS. The first protocol is a phase 3 trial to test the therapeutic value of intravenous recombinant human keratinocyte growth factor in patients with early lung injury before they have met criteria for ARDS. These patients will be primarily identified in the Emergency Departments when they have bilateral pulmonary infiltrates on the chest radiograph and the need for more than 2 liters of supplemental oxygen, but do not yet require positive pressure ventilation. The second protocol is a phase 2b trial to test the potential therapeutic value of allogeneic, bone marrow-derived human mesenchymal stem cells for the treatment of patients with moderate to severe ARDS (PaO2/FiO2 < 200 mm Hg) in the Intensive Care Unit.